chr4-139889909-TTGCTGCTGCTGC-T

Variant names:

• chr4-139889909-TTGCTGCTGCTGC-T
• rs58015886
• NM_018717.5:c.1515_1526delGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018717.5(MAML3):​c.1515_1526delGCAGCAGCAGCA​(p.Gln506_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00486 in 1,476,404 control chromosomes in the GnomAD database, including 297 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.079 (177 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (120 hom.)
• Consequence: MAML3 NM_018717.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

Genes affected

MAML3 (HGNC:16272): (mastermind like transcriptional coactivator 3) Enables transcription coactivator activity. Involved in Notch signaling pathway and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.1515_1526delGCAGCAGCAGCA	p.Gln506_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.1515_1526delGCAGCAGCAGCA	p.Gln506_Gln509del	disruptive_inframe_deletion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1	c.1515_1526delGCAGCAGCAGCA	p.Gln506_Gln509del	disruptive_inframe_deletion	Exon 2 of 3		XP_047271886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML3	ENST00000509479.6	c.1515_1526delGCAGCAGCAGCA	p.Gln506_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-159254_109-159243delGCAGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 3750 AN: 47752 Hom.: 176 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0372

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00130

Gnomad SAS AF: 0.000780

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00545

Gnomad OTH AF: 0.0607

GnomAD3 exomes AF: 0.00692 AC: 1183 AN: 171060 Hom.: 68 AF XY: 0.00557 AC XY: 521 AN XY: 93608

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.00516

Gnomad ASJ exome AF: 0.000137

Gnomad EAS exome AF: 0.00164

Gnomad SAS exome AF: 0.000786

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00534

GnomAD4 exome AF: 0.00238 AC: 3402 AN: 1428566 Hom.: 120 AF XY: 0.00210 AC XY: 1488 AN XY: 707872

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.00449

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000979

Gnomad4 SAS exome AF: 0.000551

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000300

Gnomad4 OTH exome AF: 0.00602

GnomAD4 genome AF: 0.0787 AC: 3766 AN: 47838 Hom.: 177 Cov.: 0 AF XY: 0.0758 AC XY: 1781 AN XY: 23486

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00130

Gnomad4 SAS AF: 0.000779

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00545

Gnomad4 OTH AF: 0.0604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58015886; hg19: chr4-140811063;